During the last year, we have developed structural models of the transmembrane and extracellular segments of Shaker, KvAP, hERG, and NaChBac channels in resting, open, and numerous transition conformations. Molecular dynamic simulations of these channels embedded in a lipid bilayer were performed to evaluate and refine the models. The models were constrained by recently obtained experimental data; e.g., the crystal structure of the Kv1.2 channel, electron paramagnetic resonance (EPR) studies of KvAP channels, thermodynamic cyclic mutagenesis studies of the binding of BeKM1 toxin from scorpions to the hERG channel, and cysteine scanning mutagenesis (SCAM) studies of Ca2+ channel pores. We have demonstrated that the 'helical screw' model for the voltage-dependent movement of the S4 voltage-sensor segment that we proposed first in 1986, is consistent with virtually all experimental results and with energetic criteria, including analyses using molecular dynamic simulations. The NaChBac channel is a prokaryotic Na+ channel that has similarities to K+, Ca2+, and Na+ channels. We were the first group to identify this sequence in the prokaryotic sequence data base. Since then, it has been expressed and its properties have been studied expensively. Efforts are underway to solve its crystal structure. We developed models of NaChBac, primarily to use it as a stepping stone to model more complex eukaryotic Ca2+ and Na+ channels. We have used the NaChBac models as template structures to develop homology models of human and fungal Ca2+ channels. We are collaborating with experimentalists to test these models and to use them to analyze the molecular pharmacology of Ca2+ channel blockers.